CN116942663A - 用于治疗hbv的化合物 - Google Patents

Info

Publication number

CN116942663A

CN116942663A CN202310780889.9A CN202310780889A CN116942663A CN 116942663 A CN116942663 A CN 116942663A CN 202310780889 A CN202310780889 A CN 202310780889A CN 116942663 A CN116942663 A CN 116942663A

Authority

CN

China

Prior art keywords

substituted

oxo

carboxylic acid

naphthyridine

pyrido

Prior art date

2017-10-05

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 262
• 238000011282 treatment Methods 0.000 title description 31
• 239000000427 antigen Substances 0.000 claims abstract description 25
• 108091007433 antigens Proteins 0.000 claims abstract description 23
• 102000036639 antigens Human genes 0.000 claims abstract description 23
• -1 3-methoxypropoxy Chemical group 0.000 claims description 418
• 125000000217 alkyl group Chemical group 0.000 claims description 172
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 119
• 125000003545 alkoxy group Chemical group 0.000 claims description 103
• 150000003839 salts Chemical class 0.000 claims description 88
• 239000001257 hydrogen Substances 0.000 claims description 83
• 229910052739 hydrogen Inorganic materials 0.000 claims description 83
• 229910052736 halogen Inorganic materials 0.000 claims description 79
• 150000002367 halogens Chemical class 0.000 claims description 79
• UHZMGDSDDXRFJY-UHFFFAOYSA-N 6H-pyrido[1,2-h][1,7]naphthyridine-10-carboxylic acid Chemical compound C1C=C2C=CC=NC2=C3N1C=CC(=C3)C(=O)O UHZMGDSDDXRFJY-UHFFFAOYSA-N 0.000 claims description 39
• 208000006454 hepatitis Diseases 0.000 claims description 21
• 208000002672 hepatitis B Diseases 0.000 claims description 20
• 239000003795 chemical substances by application Substances 0.000 claims description 17
• 241000124008 Mammalia Species 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 11
• OERUXIYQWSPQPV-UHFFFAOYSA-N 6-tert-butyl-2-chloro-3-(cyclopropylmethoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)C1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)Cl)OCC1CC1 OERUXIYQWSPQPV-UHFFFAOYSA-N 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 239000003443 antiviral agent Substances 0.000 claims description 6
• FOVBKYCDESHFKQ-UHFFFAOYSA-N 2-chloro-3-(cyclopropylmethoxy)-10-oxospiro[5H-pyrido[1,2-h][1,7]naphthyridine-6,1'-cyclobutane]-9-carboxylic acid Chemical compound ClC1=NC=2C=3N(C4(CC=2C=C1OCC1CC1)CCC4)C=C(C(C=3)=O)C(=O)O FOVBKYCDESHFKQ-UHFFFAOYSA-N 0.000 claims description 5
• HZLWVMLWHXTONK-UHFFFAOYSA-N 2-chloro-3-(cyclopropylmethoxy)-6-methyl-10-oxo-6-propan-2-yl-5H-pyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound ClC1=NC=2C=3N(C(CC=2C=C1OCC1CC1)(C)C(C)C)C=C(C(C=3)=O)C(=O)O HZLWVMLWHXTONK-UHFFFAOYSA-N 0.000 claims description 5
• XJYCVIAPOBSBLW-UHFFFAOYSA-N 2-chloro-6-(1-hydroxy-2-methylpropan-2-yl)-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound ClC1=NC=2C=3N(C(CC=2C=C1OCCCOC)C(CO)(C)C)C=C(C(C=3)=O)C(=O)O XJYCVIAPOBSBLW-UHFFFAOYSA-N 0.000 claims description 5
• 230000000840 anti-viral effect Effects 0.000 claims description 5
• KOJUXBZPJIUTDM-KRWDZBQOSA-N (6S)-6-tert-butyl-2-chloro-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)Cl)OCCCOC KOJUXBZPJIUTDM-KRWDZBQOSA-N 0.000 claims description 4
• XUKJCOWZQBSPLG-FQEVSTJZSA-N (6S)-6-tert-butyl-2-cyclopropyl-3-(cyclopropylmethoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C1CC1)OCC1CC1 XUKJCOWZQBSPLG-FQEVSTJZSA-N 0.000 claims description 4
• LQZPBLIRTWNKQM-FQEVSTJZSA-N (6S)-6-tert-butyl-3-(3-methoxypropoxy)-10-oxo-2-prop-1-en-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C(=C)C)OCCCOC LQZPBLIRTWNKQM-FQEVSTJZSA-N 0.000 claims description 4
• BBHIHMBNUWHAPU-IBGZPJMESA-N (6S)-6-tert-butyl-3-(3-methoxypropoxy)-2-methyl-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C)OCCCOC BBHIHMBNUWHAPU-IBGZPJMESA-N 0.000 claims description 4
• MOOBNOCKGZQCKI-SFHVURJKSA-N (6S)-6-tert-butyl-3-(cyclopropylmethoxy)-2-methoxy-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)OC)OCC1CC1 MOOBNOCKGZQCKI-SFHVURJKSA-N 0.000 claims description 4
• SHKVORNTVZIFEY-IBGZPJMESA-N (6S)-6-tert-butyl-3-(cyclopropylmethoxy)-2-methyl-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C)OCC1CC1 SHKVORNTVZIFEY-IBGZPJMESA-N 0.000 claims description 4
• CVSKFRQVNUAQFL-UHFFFAOYSA-N 2,3-dimethoxy-10-oxospiro[5H-pyrido[1,2-h][1,7]naphthyridine-6,1'-cyclobutane]-9-carboxylic acid Chemical compound COC1=NC=2C=3N(C4(CC=2C=C1OC)CCC4)C=C(C(C=3)=O)C(=O)O CVSKFRQVNUAQFL-UHFFFAOYSA-N 0.000 claims description 4
• YPFUTXUPLOKMMH-IBGZPJMESA-N (6S)-6-tert-butyl-2-(hydroxymethyl)-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)CO)OCCCOC YPFUTXUPLOKMMH-IBGZPJMESA-N 0.000 claims description 3
• UUCAYEMTRZHJRR-KRWDZBQOSA-N (6S)-6-tert-butyl-2-cyclopropyl-11-hydroxy-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2O)=O)C(=O)O)C1CC1)OCCCOC UUCAYEMTRZHJRR-KRWDZBQOSA-N 0.000 claims description 3
• XFVFUUCOPWQAHQ-FQEVSTJZSA-N (6S)-6-tert-butyl-2-cyclopropyl-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C1CC1)OCCCOC XFVFUUCOPWQAHQ-FQEVSTJZSA-N 0.000 claims description 3
• ZCKXKLRWPQGERA-FQEVSTJZSA-N (6S)-6-tert-butyl-3-(3-methoxypropoxy)-10-oxo-2-propan-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)C(C)C)OCCCOC ZCKXKLRWPQGERA-FQEVSTJZSA-N 0.000 claims description 3
• LFRQFMQMLYUYNO-UHFFFAOYSA-N 2-cyclopropyl-3-(3-methoxypropoxy)-6-methyl-10-oxo-6-propan-2-yl-5H-pyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C1(CC1)C1=NC=2C=3N(C(CC=2C=C1OCCCOC)(C)C(C)C)C=C(C(C=3)=O)C(=O)O LFRQFMQMLYUYNO-UHFFFAOYSA-N 0.000 claims description 3
• UBXAHBHUVGJQIJ-SFHVURJKSA-N (6S)-6-tert-butyl-2-methoxy-3-(3-methoxypropoxy)-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylic acid Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)O)OC)OCCCOC UBXAHBHUVGJQIJ-SFHVURJKSA-N 0.000 claims description 2
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
• 241000700721 Hepatitis B virus Species 0.000 abstract description 61
• 238000000034 method Methods 0.000 abstract description 57
• 241000724709 Hepatitis delta virus Species 0.000 abstract description 15
• 239000003112 inhibitor Substances 0.000 abstract description 11
• 239000000203 mixture Substances 0.000 description 205
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 184
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 169
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 152
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 149
• 239000011541 reaction mixture Substances 0.000 description 148
• 125000001072 heteroaryl group Chemical group 0.000 description 144
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
• 239000000243 solution Substances 0.000 description 135
• 239000007787 solid Substances 0.000 description 111
• 229910052757 nitrogen Inorganic materials 0.000 description 105
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 103
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 103
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 102
• 125000003118 aryl group Chemical group 0.000 description 97
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
• 125000005842 heteroatom Chemical group 0.000 description 87
• 235000002639 sodium chloride Nutrition 0.000 description 85
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
• 150000002431 hydrogen Chemical class 0.000 description 73
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 70
• 238000005481 NMR spectroscopy Methods 0.000 description 67
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 65
• 125000003107 substituted aryl group Chemical group 0.000 description 65
• 235000019439 ethyl acetate Nutrition 0.000 description 61
• 125000003342 alkenyl group Chemical group 0.000 description 57
• 125000000547 substituted alkyl group Chemical class 0.000 description 57
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 55
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 52
• 239000000460 chlorine Substances 0.000 description 51
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 50
• 235000019253 formic acid Nutrition 0.000 description 50
• 125000005017 substituted alkenyl group Chemical group 0.000 description 50
• 238000006243 chemical reaction Methods 0.000 description 47
• 239000012044 organic layer Substances 0.000 description 47
• 229910052760 oxygen Inorganic materials 0.000 description 47
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
• 125000005415 substituted alkoxy group Chemical class 0.000 description 43
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 42
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 40
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 37
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
• 239000012267 brine Substances 0.000 description 36
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 36
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
• 239000002904 solvent Substances 0.000 description 35
• 125000001424 substituent group Chemical group 0.000 description 35
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 33
• 239000011734 sodium Substances 0.000 description 33
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 32
• 239000002609 medium Substances 0.000 description 32
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 31
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 28
• 229910052727 yttrium Inorganic materials 0.000 description 28
• 239000000843 powder Substances 0.000 description 27
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 27
• 239000000706 filtrate Substances 0.000 description 26
• 229910052721 tungsten Inorganic materials 0.000 description 26
• 229910052799 carbon Inorganic materials 0.000 description 25
• 125000000623 heterocyclic group Chemical group 0.000 description 25
• 208000015181 infectious disease Diseases 0.000 description 25
• 239000008194 pharmaceutical composition Substances 0.000 description 25
• 239000003921 oil Substances 0.000 description 24
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 23
• 230000002829 reductive effect Effects 0.000 description 23
• 238000001914 filtration Methods 0.000 description 22
• 235000019198 oils Nutrition 0.000 description 22
• 229910052938 sodium sulfate Inorganic materials 0.000 description 22
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 21
• 238000010898 silica gel chromatography Methods 0.000 description 21
• 235000011152 sodium sulphate Nutrition 0.000 description 21
• 125000003396 thiol group Chemical class [H]S* 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
• 229910000027 potassium carbonate Inorganic materials 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• 235000011181 potassium carbonates Nutrition 0.000 description 19
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 19
• 230000009385 viral infection Effects 0.000 description 19
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 238000001035 drying Methods 0.000 description 18
• 238000009472 formulation Methods 0.000 description 18
• 208000036142 Viral infection Diseases 0.000 description 17
• 125000005843 halogen group Chemical group 0.000 description 17
• 231100000283 hepatitis Toxicity 0.000 description 17
• 239000012071 phase Substances 0.000 description 17
• 239000000741 silica gel Substances 0.000 description 17
• 229910002027 silica gel Inorganic materials 0.000 description 17
• 229910052717 sulfur Inorganic materials 0.000 description 17
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 238000004440 column chromatography Methods 0.000 description 15
• 239000012043 crude product Substances 0.000 description 14
• 125000004093 cyano group Chemical group *C#N 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• 235000011056 potassium acetate Nutrition 0.000 description 14
• 238000000746 purification Methods 0.000 description 14
• 239000012453 solvate Substances 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• 238000002560 therapeutic procedure Methods 0.000 description 14
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
• 125000004103 aminoalkyl group Chemical group 0.000 description 13
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 13
• 238000004587 chromatography analysis Methods 0.000 description 13
• BOJLXWSIMUEPCI-UHFFFAOYSA-N ethyl 4-oxopyran-3-carboxylate Chemical compound O=C1C(=COC=C1)C(=O)OCC BOJLXWSIMUEPCI-UHFFFAOYSA-N 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
• KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 12
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 12
• 229920006395 saturated elastomer Polymers 0.000 description 12
• 125000004001 thioalkyl group Chemical group 0.000 description 12
• 229910021605 Palladium(II) bromide Inorganic materials 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 210000004369 blood Anatomy 0.000 description 11
• 239000008280 blood Substances 0.000 description 11
• 125000004432 carbon atom Chemical group C* 0.000 description 11
• 201000010099 disease Diseases 0.000 description 11
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• OHENQANLQNOMAO-UHFFFAOYSA-N oxaborole Chemical group O1B=CC=C1 OHENQANLQNOMAO-UHFFFAOYSA-N 0.000 description 11
• INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• 230000002441 reversible effect Effects 0.000 description 11
• 239000000377 silicon dioxide Substances 0.000 description 11
• 208000037262 Hepatitis delta Diseases 0.000 description 10
• 239000003480 eluent Substances 0.000 description 10
• 238000010828 elution Methods 0.000 description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 208000029570 hepatitis D virus infection Diseases 0.000 description 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
• 210000002966 serum Anatomy 0.000 description 10
• 238000006467 substitution reaction Methods 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 230000003612 virological effect Effects 0.000 description 10
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
• 238000001704 evaporation Methods 0.000 description 9
• 239000011630 iodine Substances 0.000 description 9
• 239000001301 oxygen Substances 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 9
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 9
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• BSSPKXNYAZZBOP-QFIPXVFZSA-N ethyl (6S)-6-tert-butyl-3-(3-methoxypropoxy)-10-oxo-2-prop-1-en-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylate Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)OCC)C(=C)C)OCCCOC BSSPKXNYAZZBOP-QFIPXVFZSA-N 0.000 description 1
• NAHJWRJIKMVPQO-QFIPXVFZSA-N ethyl (6S)-6-tert-butyl-3-(3-methoxypropoxy)-10-oxo-2-propan-2-yl-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylate Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)OCC)C(C)C)OCCCOC NAHJWRJIKMVPQO-QFIPXVFZSA-N 0.000 description 1
• PCTFASXREWHJSC-FQEVSTJZSA-N ethyl (6S)-6-tert-butyl-3-(cyclopropylmethoxy)-2-methoxy-10-oxo-5,6-dihydropyrido[1,2-h][1,7]naphthyridine-9-carboxylate Chemical compound C(C)(C)(C)[C@@H]1CC=2C=C(C(=NC=2C=2N1C=C(C(C=2)=O)C(=O)OCC)OC)OCC1CC1 PCTFASXREWHJSC-FQEVSTJZSA-N 0.000 description 1
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